ORIENTAL, NC, United States
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Thornton M.,Endra Inc | Stantz K.,Purdue University | Kruger R.,Optosonics, Inc.
Medical Physics | Year: 2011

Purpose: Employ volumetric photoacoustic computed tomography (PA‐CT) imaging to monitor key indices of tumor biology in tumor bearing mice without the use of exogenous contrast. In this study we describe the scanning system and its use in tracking in vivo tumor vasculature and tumor volume, through tumor growth and following treatment by anti‐angiogenic therapy, in both control and treated animals. Methods: A PA‐CT scanner, specifically designed for mouse imaging, employs a sparse array of 128 discrete transducer elements (3mm in diameter, 5MHz center frequency) arranged on a hemispherical surface, a tunable NIR pulsed laser (680– 950nm), and a digital acquisition system with 128 channels. The tissue being imaged is illuminated directly by pulses of laser light and the resulting photoacoustic signals are recorded. The photoacoustic data is reconstructed using a modified 3‐D Radon transform to produce a spherical volume 25mm in diameter. EGFR+ MCF‐7 breast cancer cells were injected into two groups (control and treatment) of mice (n=6). The tumors were allowed to grow to approx. 10mm in size at which point the treatment group was injected with a single dose of Avastin (40mg/kg). The mice were scanned at 17, 27, and 34 days post‐implantation. Results: The tumor vascularity was quantified by measurement of hemoglobin (Hb) content in the tumor. The Avastin treated mice showed an average decrease of 65% in hemoglobin content following treatment while the control group had an average increase in tumor Hb content of 33%. Conclusions: The strong absorption of NIR light by oxy‐hemoglobin and deoxy‐hemoglobin provides a useful contrast mechanism for photoacoustic imaging without the use of exogenous contrast agents. Photoacoustic imaging is well suited to in vivo studies of cancer therapies where the tumor vasculature is a marker of the efficacy of the therapy or intervention. Funding Support, Disclosures, and Conflict of Interest: M. Thornton is an employee of Endra Inc. © 2011, American Association of Physicists in Medicine. All rights reserved.


Liu B.,Purdue University | Kruger R.,Optosonics, Inc. | Reinecke D.,Optosonics, Inc. | Stantz K.M.,Purdue University | Stantz K.M.,Indiana University
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2010

Purpose: The purpose of this study is to use PCT spectroscopy scanner to monitor the hemoglobin concentration and oxygen saturation change of living mouse by imaging the artery and veins in a mouse tail. Materials and Methods: One mouse tail was scanned using the PCT small animal scanner at the isosbestic wavelength (796nm) to obtain its hemoglobin concentration. Immediately after the scan, the mouse was euthanized and its blood was extracted from the heart. The true hemoglobin concentration was measured using a co-oximeter. Reconstruction correction algorithm to compensate the acoustic signal loss due to the existence of bone structure in the mouse tail was developed. After the correction, the hemoglobin concentration was calculated from the PCT images and compared with co-oximeter result. Next, one mouse were immobilized in the PCT scanner. Gas with different concentrations of oxygen was given to mouse to change the oxygen saturation. PCT tail vessel spectroscopy scans were performed 15 minutes after the introduction of gas. The oxygen saturation values were then calculated to monitor the oxygen saturation change of mouse. Results: The systematic error for hemoglobin concentration measurement was less than 5% based on preliminary analysis. Same correction technique was used for oxygen saturation calculation. After correction, the oxygen saturation level change matches the oxygen volume ratio change of the introduced gas. Conclusion: This living mouse tail experiment has shown that NIR PCT-spectroscopy can be used to monitor the oxygen saturation status in living small animals. © 2010 Copyright SPIE - The International Society for Optical Engineering.


Reinecke D.R.,Optosonics, Inc. | Kruger R.A.,Optosonics, Inc. | Lam R.B.,Optosonics, Inc. | Del Rio S.P.,Optosonics, Inc.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2010

We have constructed and tested a prototype test bed that allows us to form 3D photoacoustic CT images using near-infrared (NIR) irradiation (700 - 900 nm), 3D thermoacoustic CT images using microwave irradiation (434 MHz), and 3D ultrasound images from a commercial ultrasound scanner. The device utilizes a vertically oriented, curved array to capture the photoacoustic and thermoacoustic data. In addition, an 8-MHz linear array fixed in a horizontal position provides the ultrasound data. The photoacoustic and thermoacoustic data sets are co-registered exactly because they use the same detector. The ultrasound data set requires only simple corrections to co-register its images. The photoacoustic, thermoacoustic, and ultrasound images of mouse anatomy reveal complementary anatomic information as they exploit different contrast mechanisms. The thermoacoustic images differentiate between muscle, fat and bone. The photoacoustic images reveal the hemoglobin distribution, which is localized predominantly in the vascular space. The ultrasound images provide detailed information about the bony structures. Superposition of all three images onto a co-registered hybrid image shows the potential of a trimodal photoacoustic-thermoacoustic-ultrasound small-animal imaging system. © 2010 Copyright SPIE - The International Society for Optical Engineering.


Lam R.B.,Optosonics, Inc. | Kruger R.A.,Optosonics, Inc. | Reinecke D.R.,Optosonics, Inc. | DelRio S.P.,Optosonics, Inc. | And 3 more authors.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2010

We demonstrate the feasibility of optical angiography on live mice using a new photoacoustic computed tomography (PCT) scanner. The scanner uses a sparse array of discrete ultrasound detectors geometrically arranged to capture 128 simultaneous radial "projections" through a 25-mm-diameter volume of interest. Denser sets of interleaved radial projections are acquired by rotating the sparse array continuously about its vertical axis during data acquisition. The device has been designed specifically for imaging laboratory mice, which remain stationary during data collection. Angiographic data are acquired at a rate of 1280 radial projections per second following a bolus injection of 2 mg/mL of indocyanine green (ICG). © 2010 Copyright SPIE - The International Society for Optical Engineering.


Liu B.,Purdue University | Kruger R.,Optosonics, Inc. | Reinecke D.,Optosonics, Inc. | Stantz K.M.,Purdue University | Stantz K.M.,Indiana University
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2010

Purpose: The purpose of this study is to calibrate the PCT scanner to quantify the hemoglobin status utilizing a blood flow phantom. Materials and Methods: A blood circulation system was designed and constructed to control the oxygen saturation and hemoglobin concentration of blood. As a part of the circulation system, a 1.1mm FEP tube was placed in the center of imaging tank of PCT scanner as the imaging object. Photoacoustic spectra (690-950 nm) was acquired for different hemoglobin concentrations (CtHb) and oxygen saturation levels (SaO2), where the formers was formed by diluting blood samples with PBS and the latter by mixing blood with gases at different oxygen content. Monte Carlo simulations were performed to calculate the photon energy depositions in the phantom tube, which took into account photon losses in water and blood. A Kappa value which represents the energy transfer efficiency of hemoglobin molecule was calculated based on the PCT measurement and simulation result. The final SaO2 value of each blood sample was calculated based on the PCT spectrum and Kappa value. These oxygen saturation results were compared with co-oximeter measurements to obtain systematic errors. Results and Conclusion: The statistic error of calculating Kappa value from hemoglobin concentration experiment was less than 5%. The systematic error between PCT spectra analysis and co-oximeter analysis for hemoglobin oxygen saturation was -4.5%. These calibration techniques used to calculate Kappa and hemoglobin absorption spectra would be used in hypoxia measurements in tumors as well as for endogenous biomarkers studies. © 2010 Copyright SPIE - The International Society for Optical Engineering.


Kruger R.A.,Optosonics, Inc. | Lam R.B.,Optosonics, Inc. | Reinecke D.R.,Optosonics, Inc. | Del Rio S.P.,Optosonics, Inc. | Doyle R.P.,Optosonics, Inc.
Medical Physics | Year: 2010

Purpose: The authors report a noninvasive technique and instrumentation for visualizing vasculature in the breast in three dimensions without using either ionizing radiation or exogenous contrast agents, such as iodine or gadolinium. Vasculature is visualized by virtue of its high hemoglobin content compared to surrounding breast parenchyma. The technique is compatible with dynamic contrast-enhanced studies. Methods: Photoacoustic sonic waves were stimulated in the breast with a pulsed laser operating at 800 nm and a mean exposure of 20 mJ/pulse over an area of ∼20 cm 2. These waves were subsequently detected by a hemispherical array of piezoelectric transducers, the temporal signals from which were filtered and backprojected to form three-dimensional images with nearly uniform k-space sampling. Results: Three-dimensional vascular images of a human volunteer demonstrated a clear visualization of vascular anatomy with submillimeter spatial resolution to a maximum depth of 40 mm using a 24 s image acquisition protocol. Spatial resolution was nearly isotropic and approached 250 μm over a 64×64×50 mm field of view. Conclusions: The authors have successfully visualized submillimeter breast vasculature to a depth of 40 mm using an illumination intensity that is 32 times less than the maximum permissible exposure according to the American National Standard for Safe Use of Lasers. Clearly, the authors can achieve greater penetration depth in the breast by increasing the intensity and the cross-sectional area of the illumination beam. Given the 24 s image acquisition time without contrast agent, dynamic, contrast-enhanced, photoacoustic breast imaging using optically absorbing contrast agents is conceivable in the future. © 2010 American Association of Physicists in Medicine.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2014

High Definition Ultrasound for Mammography Abstract We propose to develop High Definition Ultrasound (HD-US) based on a hemispherical synthetic aperture and backscattered sonic waves. This configuration will produce direct three-dimensional maps of ultrasound reflectivity of breast tissues, and will display higher signal-to-noise, reduced speckle and greater spatial resolution compared to ultrasound arrays based on linear or curved planar sampling apertures. Our prototype hemispherical array consistsof four interdigitated sub-arrays, each having 128 discrete elements. Currently, this array is used to capture 3D photoacoustic images of the whole breast using a spiral scanning strategy to increase the field of view sufficiently to perform whole-breastscreening - PhotoAcoustic Mammography (PAM). In Phase I of this work, we will add a multiplexed pulser, pulse sequencer and T/R switches to capture ultrasound reflectivity data sufficient to form a 3D ultrasound image using the same reconstruction


Photoacoustic imaging is enhanced by scanning (61) the sensor array (10) used in photoacoustic imaging laterally relative to the tissue being imaged, gathering multiple tissue images (70, 71, 72, 73) at multiple relative lateral positions, and generating a photoacoustic image (80) of the tissue by combining the images taken at multiple relative lateral positions.


PubMed | Optosonics, Inc.
Type: Journal Article | Journal: Medical physics | Year: 2013

To report the design and imaging methodology of a photoacoustic scanner dedicated to imaging hemoglobin distribution throughout a human breast.The authors developed a dedicated breast photoacoustic mammography (PAM) system using a spherical detector aperture based on our previous photoacoustic tomography scanner. The system uses 512 detectors with rectilinear scanning. The scan shape is a spiral pattern whose radius varies from 24 to 96 mm, thereby allowing a field of view that accommodates a wide range of breast sizes. The authors measured the contrast-to-noise ratio (CNR) using a target comprised of 1-mm dots printed on clear plastic. Each dot absorption coefficient was approximately the same as a 1-mm thickness of whole blood at 756 nm, the output wavelength of the Alexandrite laser used by this imaging system. The target was immersed in varying depths of an 8% solution of stock Liposyn II-20%, which mimics the attenuation of breast tissue (1.1 cm(-1)). The spatial resolution was measured using a 6 m-diameter carbon fiber embedded in agar. The breasts of four healthy female volunteers, spanning a range of breast size from a brassiere C cup to a DD cup, were imaged using a 96-mm spiral protocol.The CNR target was clearly visualized to a depth of 53 mm. Spatial resolution, which was estimated from the full width at half-maximum of a profile across the PAM image of a carbon fiber, was 0.42 mm. In the four human volunteers, the vasculature was well visualized throughout the breast tissue, including to the chest wall.CNR, lateral field-of-view and penetration depth of our dedicated PAM scanning system is sufficient to image breasts as large as 1335 mL, which should accommodate up to 90% of the women in the United States.


Kruger R.A.,Optosonics, Inc. | Kuzmiak C.M.,University of North Carolina at Chapel Hill | Lam R.B.,Optosonics, Inc. | Reinecke D.R.,Optosonics, Inc. | And 2 more authors.
Medical Physics | Year: 2013

Purpose: To report the design and imaging methodology of a photoacoustic scanner dedicated to imaging hemoglobin distribution throughout a human breast. Methods: The authors developed a dedicated breast photoacoustic mammography (PAM) system using a spherical detector aperture based on our previous photoacoustic tomography scanner. The system uses 512 detectors with rectilinear scanning. The scan shape is a spiral pattern whose radius varies from 24 to 96 mm, thereby allowing a field of view that accommodates a wide range of breast sizes. The authors measured the contrast-to-noise ratio (CNR) using a target comprised of 1-mm dots printed on clear plastic. Each dot absorption coefficient was approximately the same as a 1-mm thickness of whole blood at 756 nm, the output wavelength of the Alexandrite laser used by this imaging system. The target was immersed in varying depths of an 8% solution of stock Liposyn II-20%, which mimics the attenuation of breast tissue (1.1 cm-1). The spatial resolution was measured using a 6 μm-diameter carbon fiber embedded in agar. The breasts of four healthy female volunteers, spanning a range of breast size from a brassiere C cup to a DD cup, were imaged using a 96-mm spiral protocol. Results: The CNR target was clearly visualized to a depth of 53 mm. Spatial resolution, which was estimated from the full width at half-maximum of a profile across the PAM image of a carbon fiber, was 0.42 mm. In the four human volunteers, the vasculature was well visualized throughout the breast tissue, including to the chest wall. Conclusions: CNR, lateral field-of-view and penetration depth of our dedicated PAM scanning system is sufficient to image breasts as large as 1335 mL, which should accommodate up to 90% of the women in the United States. © 2013 American Association of Physicists in Medicine.

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